Interactions with microbial communities can have profound influences on animal physiology, thereby impacting animal performance and fitness. Therefore, it is important to understand the diversity and nature of host-microbe interactions in various animal groups (invertebrates, fish, amphibians, reptiles, birds, and mammals).
Microbial communities contribute to a wide variety of biological functions in hosts and have the ability to specifically influence the health of those organisms through production of specialized metabolites. However, the structures or molecular mechanisms related to health or disease in host-microbe interactions represent a knowledge gap.
There are more than one million microbial cells in every drop of seawater, and their collective metabolisms not only recycle nutrients that can then be used by larger organisms but also catalyze key chemical transformations that maintain Earth’s habitability. Understanding how these microbes interact with each other and with multicellular hosts is critical to reliably quantify any functional aspect of their metabolisms and to predicting their outcomes on larger scales.
Engineering microbial systems allows the generation of new technologies having significant impact in the biotechnological industry and on human health. In the past few years, several synthetic biology approaches have been implemented in bacteria to allow precise engineering of novel regulatory circuits for several applications.
An enduring theme in microbial ecology is the interdependence of microbial community members. Interactions between community members include provision of cofactors, establishment of redox gradients, and turnover of key nutrients to drive biogeochemical cycles.
Severe bacterial pneumonia is a major global cause of morbidity and mortality, yet current diagnostic approaches rely on identification of causative pathogens by cultures, which require extended incubation periods and often fail to detect relevant pathogens. Consequently, patients are prescribed broad-spectrum antibiotics in a “one-size-fits-all” manner, which may be inappropriate for their individual needs and promote antibiotic resistance.
Although the importance of human genetic polymorphisms in therapeutic outcomes is well established, the role of specific genotypic or copy number variants in our “second genome” (the microbiome) has been largely overlooked. In this Perspective, I will discuss three major barriers to integrating metagenomics into pharmacology, highlighting ongoing research by us and others that has begun to shed light on the mechanisms that link the human microbiome to the efficacy and toxicity of small-molecule and biological therapies.
Over the last decades, sequencing technologies have transformed our ability to investigate the composition and functional capacity of microbial communities. Even so, critical questions remain about these complex systems that cannot be addressed by the bulk, community-averaged data typically provided by sequencing methods.
The importance of Brazil as a producer and exporter of food and feed will continuously increase. Despite the recent economic and political problems in Brazil, the scientific field is expanding.
Microbiomes underpin biogeochemical processes, sustain the bases of food webs, and recycle carbon and nutrients. Thus, microbes are frontline players in determining ecosystem responses to environmental change.
Despite growing efforts to understand the role of the microbiota in airway disease, mechanisms that link microbial community dysbiosis to chronic inflammation remain elusive. Our laboratory is interested in how altered microbiota composition or function influences airway inflammatory diseases, including chronic rhinosinusitis, asthma, and cystic fibrosis.
Despite increasing acknowledgment that microorganisms underpin the healthy functioning of basically all multicellular life, few cross-disciplinary teams address the diversity and function of microbiota across organisms and ecosystems. Our newly formed consortium of junior faculty spanning fields such as ecology and geoscience to mathematics and molecular biology from the University of Hawai‘i at Mānoa aims to fill this gap.
Natural products are the richest source of chemical compounds for drug discovery. Particularly, bacterial secondary metabolites are in the spotlight due to advances in genome sequencing and mining, as well as for the potential of biosynthetic pathway manipulation to awake silent (cryptic) gene clusters under laboratory cultivation.
As troves of microbiome sequencing data provide improved resolution of patterns of microbial diversity, new approaches are needed to understand what controls these patterns. Many microbial ecologists are using cultivated model microbial communities to address this challenge.
Over the past 2 decades, molecular techniques have established the critical role of both free-living and host-associated microbial partnerships in the environment. Advancing research to link microbial community dynamics simultaneously to host physiology and ecosystem biogeochemistry is required to broaden our understanding of the ecological roles of environmental microbes.
Microbiome studies typically focus on characterizing the taxonomic and functional profiles of the microbes within a community. Functional profiling is generally thought to be superior to taxonomic profiling for investigating human-microbe interactions, but there are several limitations and challenges to existing approaches.
The hologenome concept of evolution is a hypothesis explaining host evolution in the context of the host microbiomes. As a hypothesis, it needs to be evaluated, especially with respect to the extent of fidelity of transgenerational coassociation of host and microbial lineages and the relative fitness consequences of repeated associations within natural holobiont populations.
A key challenge in microbiology will be developing tools for manipulating human gut bacterial communities. Our ability to predict and control the dynamics of these communities is now in its infancy.
I imagine a future in which children grow up with healthy microbial communities. Engineering human microbiomes might actually be achievable in the near future, as we enter an era of hunting for human-adapted bacterial strains and phages. Furthermore, breath metabolites could allow us to track whether a probiotic colonizes persistently or a phage has knocked down a microbe of interest.
To improve predictions of ecosystem function in future environments, we need to integrate the ecological and environmental histories experienced by microbial communities with hydrobiogeochemistry across scales. A key issue is whether we can derive generalizable scaling relationships that describe this multiscale integration.
Insect-vectored pathogens pose one of the greatest threats to plant and animal, including human, health on a global scale. Few effective control strategies have been developed to thwart the transmission of any insect-transmitted pathogen.
Rational microbiome-based therapies may one day treat a wide range of diseases and promote wellness. Yet, we are still limited in our abilities to employ such therapies and to predict which bacterial strains have the potential to stably colonize a person.
Over the past 10 years, microbiome research has focused on defining the structures associated with different disease states in multiple systems, but has fallen short on showing causation. Prior omic studies have generated many new hypotheses, but moving forward we need to start dissecting the function of each bacterium alone and in concert with complex bacterial communities in well-characterized systems.
Darwin referred to life as a struggle. Organisms compete for limited resources in nature, and their traits influence the outcome.
Microbes occupy diverse habitats, forming interconnected, dynamic communities. Elucidating the principles of microbial community function is a grand challenge for microbiology, and it will entail experiments that engage microbiomes across multiple levels of complexity.
Animals evolved in a world teeming with microbes, which play pivotal roles in their health, development, and evolution. Although the overwhelming majority of living animals are invertebrates, the minority of “microbiome” studies focus on this group.
The methane concentration in the Earth’s atmosphere is rising, and, as methane is a potent greenhouse gas, it contributes considerably to climate change. It is produced by methanogenic archaea that thrive in anoxic habitats and can be oxidized by methane-oxidizing bacteria or archaea.
Microbial and plant specialized metabolites, also known as natural products, are key mediators of microbe-microbe and host-microbe interactions and constitute a rich resource for drug development. In the past decade, genome mining has emerged as a prominent strategy for natural product discovery.
In recent years, there has been a deluge of papers linking altered microbiome compositions to a myriad of diseases. Mechanistic insight into microbial drivers of disease phenotypes is essential for translation to novel therapies.
Bacteria have supplied us with many bioactive molecules for use in medicine and agriculture. However, rates of discovery have decreased as the biosynthetic capacity of the culturable biosphere has been continuously mined for many decades.
The human gastrointestinal tract harbors a diverse, highly mutualistic microbial flora which could produce a myriad of specialized metabolites. These specialized metabolites are the chemical cellphones that gut microflora use to communicate with their human host and could potentially be used to cure diseases.
Metagenomics has transformed microbiology, but its potential has not been fully expressed yet. From computational methods for digging deeper into metagenomes to study designs for addressing specific hypotheses, the Segata Lab is pursuing an integrative metagenomic approach to describe and model human-associated microbial communities as collections of strains.
The Waldron lab for computational biostatistics bridges the areas of cancer genomics and microbiome studies for public health, developing methods to exploit publicly available data resources and to integrate -omics studies.
Human-associated microbial communities include prokaryotic and eukaryotic organisms across high-level clades of the tree of life. While advances in high-throughput sequencing technology allow for the study of diverse lineages, the vast majority of studies are limited to bacteria, and very little is known on how eukaryote microbes fit in the overall microbial ecology of the human gut.